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Obstructive Sleep Apnea–Hypopnea and Incident Stroke

The Sleep Heart Health Study

¹ Department of Medicine, Case Western Reserve University, Cleveland, Ohio; ² Department of Biostatistics, and ¹² Department of Medicine, Johns Hopkins University, Baltimore, Maryland; ³ Boston University School of Medicine, Boston, Massachusetts; ⁴ VA Boston Healthcare System, Boston, Massachusetts; ⁵ Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona; ⁶ American Association of Homes and Services for the Aging and ⁷ Department of Medicine, Georgetown University, Washington, DC; ⁸ Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (retired); ⁹ Division of General Internal Medicine, University of California, Davis, California; ¹⁰ Center for American Indian Health Research, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; ¹¹ Department of Medicine, University of Arizona College Of Medicine, Tucson, Arizona

Correspondence and requests for reprints should be addressed to Susan Redline, M.D., M.P.H., Brigham and Women's Hospital, 221 Longwood Ave., Boston, MA 02115. E-mail: susan.redline{at}gmail.com

Rationale: Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population.

Objectives: To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea.

Methods: Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea–hypopnea index (OAHI) and outcome was incident ischemic stroke.

Measurements and Main Results: A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1–7.4). In the mild to moderate range (OAHI, 5–25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2–10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25.

Conclusions: The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.

Key Words: sleep apnea • stroke • epidemiology

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Obstructive sleep apnea is a common health problem and is frequently associated with cardiovascular morbidity. Prior studies have not addressed the risk of stroke attributable to sleep apnea in the general population. What This Study Adds to the Field This study addresses whether sleep apnea is associated with an increased risk of ischemic stroke in men and women recruited from the community. This study provides compelling evidence, based on 8 years of prospective data from a large, geographically diverse community-based cohort of middle-aged and older adults, that modest to severe levels of sleep apnea are associated with an approximately threefold increase risk of ischemic stroke in men.